Background: Biologically derived porcine secretin has been clinically used for many years as a diagnostic agent to assess exocrine pancreas function, facilitate the cytological diagnosis of pancreatic cancer and diagnose gastrinoma. A pure synthetic porcine secretin is now available for investigational clinical use. This study compared the pharmacology of synthetically (sPS) and biologically (bPS) derived porcine secretins in normal volunteers. Methods: Secretin stimulation tests were performed in 12 healthy normal male and female volunteer subjects in a double blind, randomized, Latin square crossover design study comparing 3 doses of synthetic porcine secretin (0.05, 0.2, and 0.4 ug/Kg) with a standard dose of biologically derived porcine secretin (1 U/Kg). A double lumen tube was placed with fluoroscopic guidance into the stomach and duodenum. Baseline duodenal aspirates were collected for two 10-minute samples prior to dosing. Four aliquots were collected from 0 to 10, 10 to 20, 20 to 40, and 40 to 60 minutes after dosing. Samples were analyzed for total volume and for bicarbonate concentration. Total bicarbonate output was calculated. Results: Twelve subjects (4 males and 8 females) completed all four treatments and were analyzed. Results by treatment, volume, and bicarbonate are tabulated below. A multiple comparison test was used to compare treatment groups. The 3 escalating doses of sPS produced a linear dose response for total volume, but similar results for bicarbonate concentration from 0 to 60 minutes. The 0.2 and 0.4 ug/Kg doses of sPS were not different from the 1 U/Kg dose of bPS for volume bicarbonate concentration and total bicarbonate output from 0 to 60 minutes. Baseline adjusted bicarbonate concentration from 0 to 60 minutes was not statistically different for any treatment. Only one patient had an adverse event, which was mild, transient flushing after the 0.2 and 0.4 ug/Kg doses of sPS and after the 1 U/Kg dose of bPS. Conclusions: SPS has identical pharmacologic effects to bPS in normal subjects. For sPS, there was a near maximal stimulation of HCO3 concentration at all doses. SPS (0.2 ug/Kg) and bPS (1 U/Kg) produced statistically equivalent and almost identical results. Both drugs were safe and well tolerated. This study validates sPS as a substitute for bPS.